Skin cancer is the most common of all cancers in the United States. Melanoma, a cancer originating in melanocytes, accounts for a relatively small percentage of skin cancers. However, melanoma causes the most skin cancer deaths making it one of the most dangerous types of skin cancer. In 2012, melanoma will account for more than 75,000 skin cancer cases.
Melanocytes also are found in organs other than skin, including the eye (e.g., in or on the uvea, ciliary body, conjunctiva, eyelid, iris, or orbit), the inner ear, meninges, bones, and heart. Ocular melanoma is the most common type of eye tumor in adults and the second most common type of primary malignant melanoma in the body. Ocular melanoma has an incidence of about five cases per one-million people in the United States.
To diagnose melanoma, suspect tissue is biopsied and examined under a microscope by a pathologist, preferably (but often not) one who is specially trained to identify melanoma in tissue biopsies. If the pathologist reports finding a melanoma, a number of factors (including the depth of the tumor in millimeters, the presence or absence of ulceration, the mitotic rate, and/or whether the tumor has spread) are used in determining a person's prognosis and course of treatment(s). When the tumor has not spread, a wider local excision is often performed to ensure that the entire lesion was removed along with a clear margin of normal tissue around the melanoma. If more extreme treatments are indicated, the patient also may receive lymphadenectomy, immunotherapy, chemotherapy, or radiation therapy.
Melanoma is almost always curable when it is found in its very early stages. Unfortunately, misdiagnoses of this disease are common (Piepkorn et al., J. Am. Acad. Dermatol., 30:707, 1994; Farmer et al., Hum. Pathol., 27:528, 1996; Corona et al., J. Clin. Oncol. 14:1218, 1996; Barnhill et al., Hum. Pathol., 30:513, 1990; Brochez et al., J. Pathol. 196:459, 2002). Diagnostic errors have a number of root causes (e.g., see Ruiter et al., Sem. Cutaneous Med. Surg., 22:33, 2003), including difficulties in differentiating between benign melanocytic nevi and early melanoma and between atypical and dysplastic nevi.
Mistakes in melanoma diagnosis have a significant adverse impact on the patients, their families, and society in general. Patients mistakenly diagnosed with a melanoma may undergo inappropriate and potentially dangerous therapy(ies), may live a life in constant fear of relapse, and may not be able to obtain life or health insurance. On the other hand, patients mistakenly diagnosed with a nevus instead of a melanoma are deprived of appropriate therapy for their malignancy, and may have their lives prematurely cut short. Finally, the societal toll of this problem is demonstrated by the fact that misdiagnosis of melanoma is the second only to misdiagnosis of breast cancer as the most common reason for cancer-based medical malpractice claims in the United States (McDonald et al., Internet J. Fam. Practice, 7(2), 2009; Troxel, Am. J. Surg. Pathol., 27:1278, 200).
Given the limitations of histopathology alone, it is of critical importance in medical science to have additional tools for the proper diagnosis of melanoma. In particular, tools are needed to determine which biopsies (e.g., dysplastic or indeterminate nevi) may, in fact, be misdiagnosed melanoma, and/or which biopsies (e.g., nevi) may demonstrate molecular characteristics of melanoma or progression to melanoma.